Post Dawn E, Fulci Giulia, Chiocca E Antonio, Van Meir Erwin G
Laboratory of Molecular Neuro-Oncology, Department of Neurology, Emory University School of Medicine, Atlanta,GA 30322, USA.
Curr Gene Ther. 2004 Mar;4(1):41-51. doi: 10.2174/1566523044577988.
Viruses that kill the host cell during their replication cycle have attracted much interest for the specific killing of tumor cells and this oncolytic virotherapy is being evaluated in clinical trials. The rationale for using replicative oncolytic viruses is that viral replication in infected tumor cells will permit in situ viral multiplication and spread of viral infection throughout the tumor mass thus overcoming the delivery problems of gene therapy. Improved understanding of the life cycle of viruses has evidenced multiple interactions between viral and cellular gene products, which have evolved to maximize the ability of viruses to infect and multiply within cells. Differences in viral-cell interactions between normal and tumor cells have emerged that have led to the design of a number of genetically engineered viral vectors that selectively kill tumor cells while sparing normal cells. These viruses have undergone further modifications to carry adjunct therapy genes to increase their anti-cancer abilities. Since these viruses kill cells by oncolytic mechanisms differing from standard anticancer therapies, there is an opportunity that synergistic interactions with other therapies might be found with the use of combination therapy. In this review, we focus on the oncolytic Herpes Simplex Virus-1 (HSV-1) vectors that have been examined in preclinical and clinical cancer models and their use in combination with chemo-, radio-, and gene therapies.
在复制周期中杀死宿主细胞的病毒因可特异性杀伤肿瘤细胞而备受关注，这种溶瘤病毒疗法正在临床试验中进行评估。使用复制型溶瘤病毒的基本原理是，病毒在受感染的肿瘤细胞中复制将允许病毒在原位增殖，并使病毒感染在整个肿瘤块中扩散，从而克服基因治疗的递送问题。对病毒生命周期的深入了解已证明病毒和细胞基因产物之间存在多种相互作用，这些相互作用的进化是为了最大化病毒在细胞内感染和增殖的能力。正常细胞与肿瘤细胞之间病毒 - 细胞相互作用的差异已经显现，这促使人们设计了许多基因工程病毒载体，这些载体能选择性地杀死肿瘤细胞，同时使正常细胞免受伤害。这些病毒经过进一步改造，携带辅助治疗基因以增强其抗癌能力。由于这些病毒通过与标准抗癌疗法不同的溶瘤机制杀死细胞，因此有可能通过联合治疗发现与其他疗法的协同相互作用。在这篇综述中，我们重点关注已在临床前和临床癌症模型中进行研究的溶瘤单纯疱疹病毒1型（HSV - 1）载体，以及它们与化学疗法、放射疗法和基因疗法联合使用的情况。
